Physicians are sometimes called upon to repair bone that has been damaged by disease, trauma, osseous surgery or other causes, or to cause bone material to grow where there has been no bone before, such as during a spine fusion procedure. As an outcome of that procedure, it is desirable for two or more vertebral bodies to be maintained in a specific orientation. This can be accomplished by growing a column or bridge of rigid bone between the vertebral bodies. This maintains them in a fixed position relative to each other. The repair of long bone fractures can often be accomplished merely by relocating disrupted bone elements into natural proximity and fixing them in place until they can heal together. This is the approach taken in repairing ordinary limb fractures, for example. The fractured bone is re-set, then immobilized for a period of weeks in a rigid or semi-rigid cast or splint as the fractured elements heal.
Sometimes, however, this approach is insufficient because the patient has lost some of the bone. This can happen in certain kinds of trauma where the bone is so badly shattered that it cannot feasibly be pieced together. More often, it happens as a result of disease that destroys bone mass or as the result of osseous surgery in which destruction of bone mass is unavoidable. In these cases, there is no “piece” of the patient's bone to re-set into proper position for healing. Instead, there is a void or defect that must somehow be filled, or a gap between two bone structures that needs to be filled with new bone. The filling of this defect or gap requires a material that is not only biocompatible but preferably will accept or even promote in-growing natural bone as the site heals. In such a manner, the material ideally will eventually become resorbed as new in-growing natural bone takes its place as part of the skeletal structure. Completely resorbed material eliminates the possibility for a stress riser that can occur when foreign matter remains in the skeleton, potentially giving rise to a fracture in the future.
Numerous bone replacement materials have been employed by physicians with varying degrees of success. One approach is to use bone material recovered from the patient himself, or so-called autologous bone. This approach is advantageous in that it avoids biocompatibility and bio-rejection problems. However, such an approach necessarily involves two surgical procedures, two surgical sites, and two healing processes-one for the original injury and a second for the site of the donated bone material. This means greater cost, and increased risk of infection and morbidity for a patient that is already seriously ill or injured. Also, this approach can require a great deal of time and surgical skill as the surgeon removes the donated material from the donation site, shapes and fits it to the primary site, and then repairs both sites. Finally, there is quite obviously a limit to the amount of bone in the patient's body available to be sacrificed as donor material.
Another approach uses human bone but not harvested from the patient. This is called allograft bone. Allograft bone is typically harvested from cadavers. It contains endogenous bone morphogenic proteins (“BMP”) and is available both in structurally intact and demineralized forms. Such material can become integrally incorporated into the patient's own skeletal system.
Demineralized allograft is routinely offered by commercial medical suppliers in dry granulated or powdered form of varying fineness. These dry granules or powder generally lack sufficient cohesiveness and adhesion for filling an osseous defect. Therefore, they are mixed with an appropriate carrier. The carrier in the past has sometimes been the patient's own blood or bone marrow. Such a carrier is of course plentiful at the surgical site, is biocompatible with the patient, and contains biological agents that promote new growth in the allograft bone elements suspended in it. On the other hand, using the patient's own blood necessitates a mixing step which might not be controlled precisely in the operating room to achieve the desired consistency. In addition, blood is not of the ideal consistency or viscosity for such an application.
Glycerol and other biocompatible materials have been used as alternate carriers in combination with demineralized allograft bone. Glycerol is suitable in consistency and viscosity for this application, but suffers from certain functional drawbacks. Because glycerol is water soluble, it could allow early dispersement of the suspended bone after being placed in the bone defect at the injury site.
Purified forms of human or animal derived collagen have been described previously for use in bone graft substitutes. When used by itself, in lyophilized form, collagen is not entirely suitable for use as a bone graft substitute. It resorbs too quickly to be an effective scaffold for bone accretion. In order for bone formation to occur, osteogenic cells (cells capable of producing bone) must attach to the osteoconductive substrate and begin the process of bone formation. The substrate must remain present long enough to allow bone formation to progress to the point of being self sustaining. Collagen can be chemically modified to make it less bioresorbable. Chemical cross linking agents such as formaldehyde and glutaraldehyde have been described. Unfortunately, low residual levels of these agents are cytotoxic and can affect bone formation in a negative manner.
Lyophilized collagen devices also compress, under soft tissue forces, not maintaining an adequate space for bone ingrowth to occur. In such circumstances, collagen can be used in combination with alloplast materials for maintaining an adequate “healing volume.” Even in these instances though, collagen still suffers the disadvantage of being a possible sensitizing agent in patients at risk for having an allergic response to collagen. In the case of bovine or other animal collagen, there is also a concern about the transmission of animal diseases, such as Bovine Spongiform Encephalopathy (BSE, or Mad Cow Disease) to the patient.
As a substitute for glycerol, high-molecular weight hydrogels, such as sodium hyaluronate, have been used to form a malleable bone putty which includes allograft bone powder suspended therein. Hyaluronon is a polysaccharide that occurs naturally in the body in the form of hyaluronic acid or in the salt form such as sodium hyaluronate. It is highly hydrophilic, viscous, and extremely lubricous. High-molecular weight hydrogels will allow suspension of very small particle sizes of allograft material.
However, even hydrogels may tend to disperse from the bone defect site. In addition, hydrogels are not conducive to retaining the body's own fluids or bone marrow aspirate which may be delivered to the defect site. There is therefore a need in the art for an improved bone graft substitute that overcomes these and other deficiencies.